CHEM 232 Reduction of Vanillin with Sodium Borohydride Lab Report

CHEM 232 f22 – Lab 4 – Experiment 28 – Reduction of VanillinVanillin is a fragrant molecule which is one of the main components of vanilla flavor. In this experiment, you
will develop your own procedure for reducing vanillin to vanillyl alcohol based on the information provided in
the next section about the reducing agent, sodium borohydride; the reaction, reduction of a carbonyl compound
to an alcohol; and the substrate and product.
CHO
MW (amu)
152.2
37.83
154.2
Vanillin
Sodium borohydride
Vanillyl alcohol
OCH3
mp (℃)
79
115
bp (℃)
285
400 (dec)
dec
OH
Vanillin
Sodium borohydride (NaBH4) and lithium aluminum hydride (LAH) are among the most effective and most
commonly-used reducing agents in organic reactions. Both reagents provide a hydride (H -) to allow reduction
of susceptible molecules, like carbonyl compounds. LAH is a much stronger reagent, and will react with
carbonyl compounds of all kinds to give the alcohol product. In addition, LAH will react violently with protic
molecules like alcohols and water. NaBH4 is a milder reagent, does not react with the carbonyl in carboxylic
acids, esters or amides, and can be suitable for reactions in some protic solvents like alcohols. The products of
the reaction, before workup, both involve coordination of the carbonyl oxygen to the boron to form boric acid
esters or aluminum alkoxides. These intermediates are hydrolyzed to boric acid and aluminum hydroxide, and
release the alcohol product, with acid workup:
R
R
2
1
R
R
O
2
R
2
1
R
O
2
OH
B
Al
O
R
2
O
R
1
R
1
or
O
R
2
O
R
R
1
H3O+
4x
R
1
OH
R
2
+ HO B
OH
or
OH
HO Al
OH
1
NaBH4 and LAH react with water to give boric acid and aluminum hydroxide, respectively, and contact with
sources of water, including from the air and from glassware, should be strictly avoided. To avoid reaction with
water in the air, these solid reactants are often protected with a coating of mineral oil in the bottle, or are stored
as solutions in water-free organic solvents in septum-sealed bottles. All reaction glassware should be ovendried. Drying tubes or dry atmospheres should be used to prevent reaction with water from the air. Bottles of
reagent should be stored in desiccators, and lids should be replaced immediately on bottles. Speed in
dispensing these reagents is required. Cleaning up spills immediately is required. LAH can combust if used
improperly, but NaBH4 is more user-friendly.
The reduction products shown in the table below would be achieved after an acid workup of the reaction
mixture:
Carbonyl Compound
LAH Reduction
NaBH4 Reduction
O
R
OH
Acid-base reaction; NR at
carbonyl
R
NH2
NR
R
OH
NR
R
OH
R
OH
R
O
NH2
R
O
O
R
R1
O
OH
H
R
R1
O
R1
R
R1
R
OH
R
OH
R
OH
R
OH
O
R
Cl
Stoichiometry: The overall stoichiometry of the borohydride reduction of a carbonyl compound is given by the
following general equation. Please note, the water included in this reaction equation is provided in the workup
step. For the reaction to proceed successfully, no water should actually be included during the reaction:
4RC(O)R’ + NaBH4 + 4H2O  4RCH(OH)R’ + B(OH)3 + NaOH
Notice how one NaBH4 molecule can reduce FOUR times. In practice, it is best to use a large excess of NaBH 4
to compensate for reagent that may have reacted with water as it was stored, or which might decompose through
other protic sources, prior to and during the reaction. The excess also pushes the reaction to completion more
quickly. Normally 1.5x to 2x the NaBH4 reagent necessary is added. Please take into account that one
molecule of NaBH4 can reduce 4 times when doing this calculation.
Solvents: Sodium borohydride reactions are usually carried out in dilute aqueous sodium hydroxide or in an
alcohol, such as ethanol, methanol or isopropanol. The reagent is not stable under acidic conditions, and
decomposes to the extent of about 5% per hour at room temperature under neutral conditions. If the reaction
time will be longer than 30 minutes at room temperature or above, isopropanol is the preferred solvent, but it is
harder to remove than ethanol or methanol. Acidic functional groups, like carboxylic acids or phenols, will
rapidly react with sodium borohydride with the evolution of hydrogen gas. Lithium aluminum hydride cannot
be used with anything at all protic; instead the reaction is so vigorous it can combust. LAH reactions are
usually carried out in polar aprotic solvents like ethers, or nonpolar solvents like alkanes. When it is necessary
to reduce molecules that contain acidic functional groups, enough base is added to keep the solution strongly
basic (at pH at 10 or higher in aqueous conditions), which will neutralize any problematic groups.
Reaction Setup: In most reactions with sodium borohydride, the aldehyde or ketone is dissolved in the
reaction solvent and a solution of sodium borohydride is added, with external cooling if necessary, at a slow
enough rate to keep the reaction mixture below 25℃. Higher temperatures contribute to more rapid
decomposition of the reagent, and adding the carbonyl compound to the base solution can cause undesirable
side reactions on many base-sensitive substrates. The amount of solvent should be enough to completely
dissolve the reactants and facilitate the workup of the reaction mixture. The solubility of sodium borohydride
per 100 grams of solvent is reported to be 55 g in water at 25℃, 16.4 g in methanol at 20℃, and 4.0 g in
ethanol at 20℃.
The time required to complete the reaction depends on the reaction temperature and the reactivity of the
substrate. In general, aldehydes are more reactive than ketones; and aliphatic carbonyl compounds are more
reactive than aromatic ones. Most reactions of aldehydes and ketones are complete in 30 minutes at room
temperature, but aromatic or hindered ketones may require more time or higher temperatures. For example, 4-tbutylcyclohexanone is completely reduced at room temperature in 20 minutes, but benzophenone is reduced
only by heating it at the boiling point of isopropyl alcohol for 30 minutes.
Workup: After the reaction is complete, the excess sodium borohydride must be decomposed by carefully
acidifying the solution to pH 6 or below, slowly, and with stirring. Usually about 3M HCl is good for this
process. Hydrogen gas is evolved as the sodium borohydride reacts with the acid, so there must be no flames,
and the workup must be done in an adequate fume hood, with the sash at an appropriate height.
Depending on the properties of the product and the reaction solvent used, the product can be separated from the
reaction mixture by filtration, extraction, or partial evaporation of the solvent and then extraction. If the product
is a solid that crystallizes from the reaction mixture, it can be collected by vacuum filtration. The yield of the
solid product can usually be increased by extracting the filtrate with diethyl ether or another suitable solvent,
and then drying and evaporating the ether. Liquids or water-soluble products are generally separated from the
aqueous reaction mixture by extraction with diethyl ether and recovered by evaporating the dried ether. If the
reaction solvent is an alcohol, the reaction mixture is usually concentrated by evaporating most of the alcohol.
Water can then be added, and the product can be extracted with a suitable organic solvent, like diethyl ether.
Purification: The product can be purified by any appropriate method, based on its physical state and
properties. Vanillyl alcohol is reported to be soluble in hot water, hot and cold ethanol, hot and cold ether, and
hot benzene. It is relatively insoluble in cold water and cold benzene. It tends to form supersaturated solutions
in water.
Procedure:
Develop your own procedure for this experiment and submit it to your instructor for approval. Carry out the
synthesis in the laboratory, measure the yield and melting point of the purified vanillyl alcohol, and turn it in.
Obtain the IR and 1H-NMR spectra of the product and compare them to the IR and 1H-NMR spectra of the
starting material to confirm that the expected functional group conversion has occurred. Dispose of any waste
appropriately. Calculate your percent yield and compare your results with the other students in the class.
Post Lab:
1. Draw the arrow-pushing reaction mechanism for the reaction of sodium borohydride with vanillin. It’s
only necessary to show two hydrides reacting with the molecule.
2. Write the balanced reaction equation for the decomposition of sodium borohydride in water to which
HCl has been added.
3. What would the effect be if you used an equimolar amount of sodium borohydride and vanillin for your
reaction?
4. Which solvent did you use for your reaction? What effect did that have on your yield?
5. Which purification steps did you do on your crude material? What effect did that have on your yield?